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Biomedical subjects

C M Epstein

Publications and source records attributed to C M Epstein.

At least 19 recordsLinked to original sources

Presentation of narcolepsy after 40.

To advance understanding of the clinical spectra of narcolepsy, we retrospectively reviewed the histories and clinical and polysomnographic features of 41 consecutive patients in whom this diagnosis was established in our center over 3 years. A total of 51% presented after the age of 40 years. Among the older patients, three subpopulations were noted: 1) narcolepsy/cataplexy with presentation delayed because of mild disease severity or misdiagnosis; 2) narcolepsy/cataplexy with diagnosis delayed until late-life expression of cataplexy; and 3) narcolepsy lacking cataplexy with later-life onset of excessive daytime sleepiness. Clinical, polysomnographic, and multiple sleep latency test assessments of rapid eye movement sleep dyscontrol and sleepiness were unrelated to age. This analysis identified older patients lacking cataplexy as the least severely affected narcoleptic subgroup. Narcolepsy, a continuum of phenotypes and severities that masks its recognition, should be considered in the differential diagnosis of sleepiness or transient loss of muscle tone in older patients.

Adult

Mapping transcranial magnetic stimulation (TMS) fields in vivo with MRI.

Transcranial magnetic stimulation (TMS) is a non-invasive technique for investigating brain function that uses pulsed magnetic fields created by special coils to induce localized neuronal depolarization. Despite the technique's expanding application, the exact magnetic field produced by TMS coils have never been directly measured in human subjects. Using a standard 1.5T MR scanner and TMS coils constructed from non magnetic materials, we have obtained 3D maps of the magnetic field created by TMS coils in human volunteers. Further, we mapped the combined field of two coils and demonstrated that combinations of coils might be used to focus the magnetic field to achieve improved stimulation patterns and, perhaps, reach areas out of reach of single coils.

Brain

Temporal lobe epilepsy and performance on the Wisconsin Card Sorting Test.

The replicability of previous evidence for differential performance between left and right temporal lobe epileptic patients on the Wisconsin Card Sorting Test (WCST) was evaluated in a new sample of candidates for focal resection. Many subjects obtained high scores on indices of perseveration, which are commonly thought to reflect frontal dysfunction, but there were no differences in performance between patients with language-dominant and nondominant temporal foci. The findings confirm existing evidence that performance decrements on the WCST can be associated with epileptic foci and focal lesions in nonfrontal brain lesions.

Adult

Magnetic coil suppression of extrafoveal visual perception using disappearance targets.

We used magnetic brain stimulation with a butterfly coil over the occipital lobes to study extrafoveal visual field effects in six subjects. The visual test pattern was a grid of asterisks around a central fixation point, and the target was the disappearance of one asterisk for a single frame of the video monitor. Using single magnetic pulses at stimulator outputs of 55-95%, we noted robust interference effects at latencies < or = 100 ms, peaking at approximately 50-90 ms. Suppression of visual perception occurred with both transverse and sagittal alignments of the coil. When the coil was moved laterally over either occipital lobe, perception of target disappearance was consistently suppressed in the contralateral visual field. Movement of the coil rostrally produced consistent suppression in the lower and middle field, but preferential suppression of the upper field could not be obtained. This altitudinal asymmetry may be correlated with the anatomy of the occipital lobe in relation to the scalp surface.

Attention

Magnetic coil suppression of visual perception at an extracalcarine site.

Perception of extrafoveal visual targets can be suppressed by magnetic stimulation over the occipital lobes, but the site of interference for this and similar phenomena has not been well defined. We modified a previously used technique to determine the locus of magnetic activation. Using butterfly stimulus coils of different sizes and electric field profiles, we determined a scalp position of minimum threshold and a level of stimulator output that produced 50% error rates for each coil. Intersection of the corresponding electric field profiles in air and in a saline model head was similar and identified superficial occipital cortex rather than the primary visual area as the site of perceptual suppression. Less direct analyses involving the distribution of induced electric fields produced the same conclusion. These results suggest specific hypotheses about the effects of magnetic stimulation on visual physiology.

Attention

Focal paresthesias with cervical magnetic stimulation.

Subjects undergoing cervical magnetic stimulation with an appropriate coil report focal hand paresthesias in a dermatomal distribution, but the physiologic accuracy of such subjective experiences has been uncertain. In six subjects, we used a butterfly-shaped magnetic coil to stimulate positions on the back of the neck at 1-cm intervals, constant output, and random order, while the subject-estimated location and intensity of paresthesias and sensory nerve action potentials (SNAPs) were recorded from the thumb or index finger. Three subjects each also had recording of finger accelerometry or compound motor action potentials (CMAPs) in the hand and forearm. We found a consistent correlation between subjective paresthesias and SNAPs but an appropriate anatomic divergence between paresthesias and accelerometry or CMAPs. Focal paresthesias from cervical magnetic stimulation are reliable and anatomically accurate, strengthening the hypothesis that other magnetic sensory phenomena are valid as well.

Action Potentials

Optimum stimulus parameters for lateralized suppression of speech with magnetic brain stimulation.

Rapid-rate transcranial magnetic brain stimulation produces lateralized suppression of speech output over the frontal lobe, consistent with cerebral dominance for language. But the sensitivity of magnetic speech localization has been limited, and reports are imprecise concerning the amount of discomfort involved. Using a focal magnetic coil, we evaluated the effectiveness and pain of stimulation at different intensities, orientations, and repetition rates (2 to 32 Hz) in six normal volunteers. We obtained complete and clearly lateralized speech arrest in all subjects. The best ratio of efficacy to pain occurred using slower repetition rates of 4 to 8 Hz with a horizontal alignment of the induced electric field. Lower stimulation frequency also allowed clearer distinction between speech arrest and dysarthria from tonic contraction of cranial muscles. The relative comfort and safety of stimulation at 4 Hz should allow more widespread use of magnetic speech localization in clinical and research applications.

Adult

Evaluation of 1H magnetic resonance spectroscopic imaging as a diagnostic tool for the lateralization of epileptogenic seizure foci.

The purpose of this study was to assess whether a visual examination of 1H spectroscopic images could correctly lateralize patients with intractable temporal lobe epilepsy. 20 patients with intractable temporal lobe epilepsy and 10 volunteers were included in this study. Spectroscopic images were analysed using a protocol based on visual inspection. Images of the metabolites N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate were obtained from a transverse plane oriented along the sylvian fissure. Images from each individual were evaluated independently by six reviewers. Results of the lateralization procedure obtained from the visual examinations were compared with those obtained from quantitative analysis of the spectra and with those obtained by magnetic resonance imaging (MRI), positron emission tomography (PET), neuropsychological examinations, and electroencephalographic (EEG) recordings. NAA images were found to be the most effective, amongst metabolite images, in lateralizing the epileptogenic lobe. Using the site selected for resection as the definition of the correct lateralization, 70% of the patients who underwent temporal lobectomy were correctly lateralized by the majority of the examiners using the visual inspection protocol. Based on the results of this study it is concluded that visual examination of 1H spectroscopic images is potentially valid in lateralizing patients with intractable temporal lobe seizures. Confidence in the visual interpretation increased as the difference in NAA signal intensity between the temporal lobes increased. The threshold above which the majority of the examiners correctly lateralized the patients was approximately 15% in NAA signal loss in the ipsilateral lobe.

Adolescent

Clozapine-induced EEG abnormalities and clinical response to clozapine.

The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

Adult

Abnormalities in posturography and estimations of visual vertical and horizontal in multiple sclerosis.

Twenty-seven patients with mild multiple sclerosis were tested with the dynamic posturography protocol used in the NeuroCom Equitest procedure. The purpose of this study was to determine if the standard test procedure elicited a pattern of responses that would suggest the possibility of multiple sclerosis during differential diagnosis of a patient with dysequilibrium. In addition, the patients' ability to align a light bar to vertical and horizontal was tested with the head erect and with the head tilted 45 degrees to the right and left shoulder. There was a pattern of abnormality in the Equitest motor coordination tests. Only one patient produced normal scores in both the latency and adaptation tests. No pattern of error was noted in the sensory organization tests. In the visual alignment tests, only 3 of the 27 patients tested produced values that were within normal limits for the three different head positions. Visual alignment and the motor coordination tests are not specific for multiple sclerosis, but poor performance probably indicates a disruption of the integration of visual, vestibular, and somatosensory information. Although patients with early multiple sclerosis and patients with purely vestibular disorders often have similar complaints, they have quite different profiles of abnormalities in posturography testing.

Diagnosis, Differential

Magnetic mapping of human cervical nerve roots: variation in normal subjects.

Cervical magnetic stimulation occurs preferentially at the neural foramen and is more effective with the induced electric field oriented transversely to the spine rather than vertically. This geometry suggests the possibility of mapping innervation from specific nerve roots. A "butterfly" stimulus coil, positioned horizontally, was used to determine the morphologies and amplitudes of compound motor action potentials from multiple muscles in the upper extremities of 15 normal adults. Averages of 5 responses were taken at 1 cm intervals along the cervical-thoracic spine. Needle electrodes were used to verify atypical patterns of innervation. Cervical spine X-rays allowed anatomic correlation. Rarely abductor digiti minimi was difficult to stimulate in the horizontal orientation; satisfactory responses were then obtained with the stimulator angled upward towards the side of stimulation. Averaged compound motor action potentials were reproducible, and as the stimulus coil was moved rostro-caudally they often changed morphology in well-defined patterns, suggesting an origin in different cervical nerve roots. The sequence of muscle activation in most subjects was consistent with conventional descriptions of segmental innervation, but 5 appeared to show substantial variation in the nerve roots supplying one or more muscles. Magnetic mapping may be a useful method for studying segmental innervation in human subjects.

Action Potentials

EEG in liver transplantation: visual and computerized analysis.

We prospectively evaluated 40 liver transplant candidates (including 28 recipients) with visually scored or computerized EEG. As expected, EEG frequencies rose significantly after successful transplant (P < 0.01). For all subjects, but especially for the transplant recipients, higher frequencies on computerized EEG at baseline had a strong association with survival at 18 months (P < 0.001). A logistic regression model allowed estimation of the odds for survival and indicated less than 50% long-term survival with central-occipital mean frequencies below 7.6 c/sec. Visual EEG scores closely paralleled the quantitative results, but only the latter were amenable to formal statistical analysis. EEG had much stronger predictive value for survival than serum albumin, although albumin improved more significantly in the months after transplantation.

Adult

Magnetic brain stimulation and brain size: relevance to animal studies.

Magnetic brain stimulation (MBS) is widely used for the investigation of brain function in man, but there have been only a few reports of its safety in animals. These results were predominantly benign, but the effectiveness of stimulation in animals is unclear. Because the stimulators produced obvious motor effects in humans, or had a comparable peak magnetic field strength, they were assumed to produce comparable electric field intensities and neuronal effects in animal brains. We tested this assumption using 3 stimulus coils of different sizes and design, plus 6 saline-filled spheres that spanned a range of volume from 0.5 to 1800 ml. The induced electric field diminished monotonically with decreasing radius, by factors of 4.7-6.2 at the extremes of size. Comparable results were found using a mathematical model. These results suggest that the efficiency of magnetic stimulation is drastically reduced in smaller brains, and that threshold and safety studies in some animal models may not be valid.

Animals

Assessment of the relationship of cerebral hemisphere arousal asymmetry to perceptual asymmetry.

This study examined the hypothesis that characteristic individual differences in cerebral hemisphere arousal asymmetry are related to individual differences in perceptual asymmetry observed in verbally based visual half-field tasks. The study used electrophysiological measures of arousal asymmetry rather than behaviorally derived measures (Levy, Heller, Banich, & Burton, 1983). Measures of alpha asymmetry were obtained from 20 right-handed males during a baseline relaxation condition and during a visual half-field version of the lexical decision task. Reaction time measures of perceptual asymmetry were obtained during this task. The results indicated that a basal arousal asymmetry measured at the temporal recording location during the baseline condition was significantly related to individual perceptual asymmetry during the subsequent lexical decision task. This basal arousal asymmetry was relatively stable across different task conditions. A task-related arousal asymmetry measured at the parietal location during the lexical decision task also made a significant contribution in predicting individual perceptual asymmetry. These two measures of individual arousal asymmetry were able to predict 50% of the variance in perceptual asymmetry. The implications of the results for explaining more wide-ranging individual differences in behavioral style and personality are discussed.

Adult

Quality-of-life changes and psychiatric and neurocognitive outcome after heart and liver transplantation.

A prospective study compared psychiatric, neurocognitive, and quality-of-life changes of heart and liver transplant patients. The 51 heart and 61 liver transplant candidates and recipients completed the Beck depression inventory (BDI), state-trait anxiety inventory (STAI), sickness impact profile (SIP), mini-mental state (MMS), California verbal learning test (CVLT), Wisconsin card sorting test (WCST), trailmaking test (TMT), and the impact message inventory (IMI). Data were gathered before transplant and at 3-month intervals for up to 1 year after transplant. Psychometric tests scores were correlated with electroencephalograms for the liver patients. Both groups showed significant improvements after transplant in neurocognitive functioning, depressive symptoms, and quality of life.

Adult

Induction of transient neurological dysfunction in baboons by platelet microemboli.

BACKGROUND AND PURPOSE: To investigate experimental mechanisms of reversible cerebral dysfunction, we produced transient focal cerebral ischemia in five baboons by unilateral perfusion of internal carotid territories with platelet microemboli generated endogenously. METHODS: Platelet microemboli were formed by incorporating segments of Dacron vascular graft for 1 hour as unilateral carotid arterio-arterial shunts. Platelet embolization was assessed by ultrasonography and isotopic imaging; cerebral function was evaluated by measurements of somatosensory evoked potentials and clinical motor performance. RESULTS: Platelet microemboli, detected by transcranial Doppler ultrasonography, accumulated rapidly in the shunted carotid hemispheric territory. Indium-111-labeled platelets reached a maximum value of 3.2 +/- 0.8 x 10(9) platelets in the dependent hemisphere of five animals after 20 minutes of carotid blood flow through the grafts when measured in real time by continuous scintillation camera imaging. The retained 111In-platelet microemboli cleared from the cerebral vasculature within 1 hour after removing the grafts. Corresponding blood markers of in vivo thrombus formation, beta-thromboglobulin, platelet factor 4, and fibrinopeptide A, increased eightfold to 20-fold after incorporating graft segments and normalized within 1 hour after removing the grafts. Coincidently, focal neurological function was temporarily impaired, as shown by the ipsilateral loss of somatosensory evoked potentials 5 minutes after initiating platelet microembolization, with restoration 1 hour after removing the grafts in five baboons, and contralateral hemiparesis in two recovered baboons, with complete resolution by 24 hours. CONCLUSIONS: Endogenously generated platelet microemboli accumulate transiently in the dependent cerebral circulation and produce corresponding focal neurological dysfunction that resolves within hours after microembolization.

Animals

Prediction of magnetically induced electric fields in biological tissue.

There are many potential medical applications in which it is desirable to noninvasively induce electric fields. One such application that serves as the backdrop of this work is that of stimulating neurons in the brain. The magnetic fields necessary must be quite high in magnitude, and fluctuate rapidly in time to induce the internal electric fields necessary for stimulation. Attention is focused on the calculation of the induced electric fields commensurate with rapidly changing magnetic fields in biological tissue. The problem is not a true eddy current problem in that the magnetic fields induced do not influence the source fields. Two techniques are introduced for numerically predicting the fields, each employing a different gauge for the potentials used to represent the electric field. The first method employs a current vector potential (analogous to A in classical magnetic field theory where DEL x A = B) and is best suited to two-dimensional (2-D) models. The second represents the electric field as the sum of a vector plus the gradient of a scalar field; because the vector can be determined quickly using Biot Savart (which for circular coils degenerates to an efficient evaluation employing elliptic integrals), the numerical model is a scalar problem even in the most complicated three dimensional geometry. These two models are solved for the case of a circular current carrying coil near a conducting body with sharp corners.

Brain